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Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:3.4.21.4 (
trypsin
)
42,187
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To evaluate secretion of mitogenic factors by ovine corpora lutea (CL) at several stages of development, luteal explants from days 5 (n = 12 ewes), 10 (n = 6 ewes), and 15 (n = 6 ewes) of the estrous cycle were incubated in serum-free medium for 24 h. Luteal-conditioned media (LCM) were evaluated for their ability to stimulate proliferation of endothelial, BALB/3T3, and ovarian granulosa cells. After mitogenic activity of LCM from individual animals was evaluated, pools of LCM from each day of the estrous cycle were subjected to anion-exchange, cation-exchange, and heparin-affinity chromatography to characterize mitogenic activity. Pools of LCM also were utilized for ultrafiltration, heat-treatment,
trypsin
-treatment, and immunoneutralization studies. Results demonstrated that ovine CL secrete mitogenic activity that stimulates (P less than 0.01) proliferation of endothelial (135.7 +/- 5.3% of control) and granulosa cells (188.9 +/- 2.9%) but not 3T3 (103.2 +/- 2.5%) cells. Differences between stages of luteal development were not observed. The mitogenic activity bound to diethylaminoethyl-Sephacel and heparin-agarose, but not to carboxymethyl-Sepharose, indicating that ovine luteal mitogenic factor(s) is anionic and may belong to the heparin-binding growth factor (HBGF) family. In addition, the mitogenic activity was heat-labile,
trypsin
-sensitive, and appeared to have a M(r) greater than 100,000. Mitogenic activity for endothelial cells was partially neutralized with a specific antibody against
HBGF-1
and was completely abolished with a specific antibody against HBGF-2. Moreover,
HBGF-1
and HBGF-2 were immunolocalized in histological sections of CL from days 5 (n = 5 ewes), 10 (n = 5 ewes), and 15 (n = 5 ewes) after estrus. These findings are the first report of a major mitogenic factor(s) produced by cyclic ovine CL and indicate this factor is an HBGF-2-like molecule.
...
PMID:Production of mitogenic factor(s) by ovine corpora lutea throughout the estrous cycle. 137 5
Myofibroblasts (Mfs) from rat fat tissues produced a potent endothelial cell growth factor (Mf-
ECGF
). The growth factor activity found in the conditioned media from primary cultures of Mfs, was labile to heat (80 degrees C for 10 min) and proteinase (
trypsin
), and did not bind to heparin in the presence of 0.2 M NaCl. Mf-
ECGF
was partially purified 4760-fold with a recovery of 25% from serum-free conditioned media by sequential carboxymethyl (CM) ion-exchange column chromatography and gel filtration. This Mf-
ECGF
activity was recovered from the 40 kD region of a non-reducing SDS-PAGE, and from the pH region between 6.5 and 7 of isoelectric focusing, with recoveries of 20% and 65%, respectively. These results indicated that a major portion of
ECGF
activity in the conditioned media was clearly distinct from other well-known endothelial cell growth factors including fibroblast growth factors (FGFs).
...
PMID:Identification of non heparin-binding endothelial cell growth factor from rat myofibroblasts. 161 30
Plasminogen activator inhibitor-1 (PAI-1) inhibits the tissue plasminogen activator (tPA) and urokinase activation of plasminogen to plasmin, a protease of
trypsin
-like specificity which is involved in a number of processes, including fibrinolysis, matrix degradation and angiogenesis. Both phorbol esters and cAMP elevating compounds have been shown to modulate PAI-1 and tPA expression in endothelial cell culture.
HBGF-1
(previously designated endothelial cell growth factor) stimulates endothelial cell growth in vitro and is angiogenic in vivo. We have reported that removal of
HBGF-1
from human umbilical vein endothelial cell (HUVEC) media results in an approximately 5-fold increase in PAI-1 mRNA levels and in PAI-1 protein secreted into the media by 20 h. Here we report the effects of
HBGF-1
on the phorbol ester and cAMP modulation of HUVEC PAI-1 expression. The phorbol ester PMA induced an approximate 5-fold increase in PAI-1 mRNA levels at 4 h, which returned to base line by 20 h, with or without
HBGF-1
present in the media. This increase in PAI-1 mRNA levels was mediated by an increase in PAI-1 gene transcription and was abated in the presence of cycloheximide. Treatment of cells with the adenylate cyclase activator forskolin or the phosphodiesterase inhibitor HL 725, in the presence of
HBGF-1
or immediately after its withdrawal, decreased PAI-1 mRNA levels and protein secreted into the conditioned media by 20 h. However, forskolin or HL 725 addition had little or no effect on PAI-1 mRNA when added 20 h after
HBGF-1
withdrawal. Both the PMA and
HBGF-1
modulation of PAI-1 were abolished by treatment with the protein kinase inhibitor H-7. Treatment of HUVEC with
HBGF-1
had no acute effect on intracellular inositol phosphate hydrolysis or cAMP levels. Further studies on intracellular pathways involved in
HBGF-1
modulation of PAI-1 will enhance our understanding of the role these factors play in cellular proliferation and angiogenesis.
...
PMID:Heparin-binding growth factor-1 modulation of plasminogen activator inhibitor-1 expression. Interaction with cAMP and protein kinase C-mediated pathways. 170 36
Two polypeptides from secretory products of human hepatoma cells were isolated and characterized on the basis of their stimulation of maintenance and growth of human endothelial cells in serum-free cell culture. Both factors were purified to homogeneity by a combination of reverse-phase, ion exchange, and molecular filtration high performance liquid chromatography. One factor (endothelial cell growth factor (
ECGF
-2a) had Mr approximately 6,500 and pI near 6. The second (
ECGF
-2b) had Mr = 27,000 and a pI below 4.0. Both
ECGF
-2a and
ECGF
-2b exhibited single NH2-terminal sequences. The first 25 NH2-terminal residues of
ECGF
-2a and the first 49 residues of
ECGF
-2b were determined by gas-phase microsequencing. All clearly determined residues of
ECGF
-2a were identical with human pancreatic secretory trypsin inhibitor. All assignable residues of
ECGF
-2b were identical with urinary glycoprotein proteinase inhibitor (HI-30/EDC1). Both proteins are absent or at low levels in normal plasma and urine, but appear during acute inflammatory disease and cancer. Amino acid composition of
ECGF
-2a and
ECGF
-2b was also similar to human pancreatic secretory inhibitor and HI-30/EDC1, respectively. Both
ECGF
-2a and
ECGF
-2b inhibited bovine pancreatic
trypsin
(2 micrograms/ml) by 50% at 750 ng/ml.
ECGF
-2a and
ECGF
-2b stimulated endothelial cell number at a half-maximal dose of 50 ng/ml (8 nM) and 80 to 130 ng/ml (5 to 9 nM) protein, respectively. When assayed under identical conditions, no effect of either factor on human smooth muscle cells, human hepatoma cells, or human, rat, and mouse fibroblasts could be detected.
...
PMID:Two apparent human endothelial cell growth factors from human hepatoma cells are tumor-associated proteinase inhibitors. 300 99
